Incidence rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have increased in the United States. Metabolic syndrome is recognized as a risk factor for HCC and a ...postulated one for ICC. The magnitude of risk, however, has not been investigated on a population level in the United States. We therefore examined the association between metabolic syndrome and the development of these cancers. All persons diagnosed with HCC and ICC between 1993 and 2005 were identified in the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database. For comparison, a 5% sample of individuals residing in the same regions as the SEER registries of the cases was selected. The prevalence of metabolic syndrome as defined by the U.S. National Cholesterol Education Program Adult Treatment Panel III criteria, and other risk factors for HCC (hepatitis B virus, hepatitis C virus, alcoholic liver disease, liver cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, hepatitis B virus, hepatitis C virus, alcoholic liver disease, cirrhosis, inflammatory bowel disease) were compared among persons who developed cancer and those who did not. Logistic regression was used to calculate odds ratios and 95% confidence intervals. The inclusion criteria were met by 3649 HCC cases, 743 ICC cases, and 195,953 comparison persons. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than the comparison group (17.1%, P < 0.0001). In adjusted multiple logistic regression analyses, metabolic syndrome remained significantly associated with increased risk of HCC (odds ratio = 2.13; 95% confidence interval = 1.96‐2.31, P < 0.0001) and ICC (odds ratio = 1.56; 95% confidence interval = 1.32‐1.83, P < 0.0001). Conclusion: Metabolic syndrome is a significant risk factor for development of HCC and ICC in the general U.S. population. (HEPATOLOGY 2011;)
Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable ...fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States.
Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated.
As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29-43.84), HBV (OR 11.17, 95% CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34-2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%).
The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance ...practices, and outcomes of NAFLD-related HCC.
We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients' full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients.
NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%-12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%-68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%-80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%-3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors.
NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC.
Background & Aims Serum levels of α-fetoprotein (AFP) are influenced not only by the presence of hepatocellular carcinoma (HCC), but also by the underlying severity and activity of liver disease, ...which is reflected by liver function tests. We constructed an AFP-based algorithm that included these factors to identify patients at risk for HCC, and tested its predictive ability in a large set of patients with cirrhosis. Methods We used the national Department of Veterans Affairs Hepatitis C Virus Clinical Case Registry to identify patients with cirrhosis, results from at least 1 AFP test, and 6 months of follow-up. Our algorithm included data on age; levels of aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, creatinine, and hemoglobin; prothrombin time; and numbers of platelets and white cells. We examined the operating characteristics (calibration, discrimination, predictive values) of several different algorithms for identification of patients who would develop HCC within 6 months of the AFP test. We assessed our final model in the development and validation subsets. Results We identified 11,721 patients with hepatitis C virus−related cirrhosis in whom 35,494 AFP tests were performed, and 987 patients developed HCC. A predictive model that included data on levels of AFP, ALT, and platelets, along with age at time of AFP test (and interaction terms between AFP and ALT, and AFP and platelets), best discriminated between patients who did and did not develop HCC. Using this AFP-adjusted model, the predictive accuracy increased at different AFP cutoffs compared with AFP alone. At any given AFP value, low numbers of platelets and ALT and older age were associated with increased risk of HCC, and high levels of ALT and normal/high numbers of platelets were associated with low risk for HCC. For example, the probabilities of HCC, based only on 20 ng/mL and 120 ng/mL AFP, were 3.5% and 11.4%, respectively. However, patients with the same AFP values (20 ng/mL and 120 ng/mL) who were 70 years old, with ALT levels of 40 IU/mL and platelet counts of 100,000, had probabilities of developing HCC of 8.1% and 29.0%, respectively. Conclusions We developed and validated an algorithm based on levels of AFP, platelets, and ALT, along with age, which increased the predictive value for identifying patients with hepatitis C virus−associated cirrhosis likely to develop HCC within 6 months. If validated in other patient groups, this model would have immediate clinical applicability.
Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S.
We identified a national cohort ...of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features.
A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC.
Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.
The epidemiology of gastrointestinal stromal tumor has not been well examined, and prior studies often provide conflicting results. We conducted the first population-based study to evaluate the ...incidence and survival of malignant gastrointestinal stromal tumor in the United States.
We utilized the Surveillance, Epidemiology, and End Results registry from the National Cancer Institute to identify all cases of malignant gastrointestinal stromal tumor diagnosed from 1992 to 2000. The age-adjusted incidence rates and the survival rates were calculated. Cox proportional hazards models were used to examine the risk of mortality.
Between 1992 and 2000, there were 1,458 cases of diagnosed gastrointestinal stromal tumor. The age-adjusted yearly incidence rate was 0.68/100,000. The mean age at diagnosis was 63 yr. Fifty-four percent were men and 46% were women. The incidence rate was higher among men and among Blacks. Fifty-one percent of cases were in the stomach, 36% small intestine, 7% colon, 5% rectum, and 1% in the esophagus. Fifty-three percent of cases were staged as localized, 19% regional, 23% distant, and 5% unstaged. The 1- and 5-yr relative survival rates were 80% and 45%, respectively. The Cox analysis showed that older age, Black race, advanced stage, and receipt of therapy were independent predictors of mortality.
Malignant gastrointestinal stromal tumors rare, but are more common in the older population, men, and Blacks. Risk factors for mortality include older age, Black race, advanced stage, and no surgical intervention.
Background Current risk-assessment tools for surgical site occurrence (SSO) and surgical site infection (SSI) are based on expert opinion or are not specific to open ventral hernia repairs. We aimed ...to develop a risk-assessment tool for SSO and SSI and compare its performance against existing risk-assessment tools in patients with open ventral hernia repair. Study Design A retrospective study of patients undergoing open ventral hernia repair (n = 888) was conducted at a single institution from 2000 through 2010. Rates of SSO and SSI were determined by chart review. Stepwise regression models were built to identify predictors of SSO and SSI and internally validated using bootstrapping. Odds ratios were converted to a point system and summed to create the Ventral Hernia Risk Score (VHRS) for SSO and SSI, respectively. Area under the receiver operating characteristic curve was used to compare the accuracy of the VHRS models against the National Nosocomial Infection Surveillance Risk Index, Ventral Hernia Working Group (VHWG) grade, and VHWG score. Results The rates of SSO and SSI were 33% and 22%, respectively. Factors associated with SSO included mesh implant, concomitant hernia repair, dissection of skin flaps, and wound class 4. Predictors of SSI included concomitant repair, dissection of skin flaps, American Society of Anesthesiologists class ≥3, wound class 4, and body mass index ≥40. The accuracy of the VHRS in predicting SSO and SSI exceeded National Nosocomial Infection Surveillance and VHWG grade, but was not better than VHWG score. Conclusions The VHRS identified patients at increased risk for SSO/SSI more accurately than the National Nosocomial Infection Surveillance scores and VHWG grade, and can be used to guide clinical decisions and patient counseling.
The incidence of hepatocellular carcinoma was reported to be increasing in the United States. However, alternate explanations were diagnostic or reclassification bias and changes in the demographic ...features of the general population.
To examine the temporal trends in the incidence of hepatocellular carcinoma.
Retrospective cohort study.
Information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program.
Persons given a diagnosis of hepatocellular carcinoma between 1975 and 1998.
Linear Poisson multivariate regression model, controlling for differences in age, sex, race or ethnicity, and geographic region among patients with hepatocellular carcinoma and in the underlying population.
The overall age-adjusted incidence rates of hepatocellular carcinoma increased from 1.4 per 100 000 in 1975 to 1977 to 3.0 per 100 000 in 1996 to 1998. There was a 25% increase during the last 3 years of the study compared with the preceding 3 years (1993 to 1995). The increase affected most age groups above 40 years, with the greatest increase in the 45- to 49-year-old age group. White men had the greatest increase (31%) in the last time period (1996 to 1998) compared with 1993 to 1995. The Poisson regression model confirmed an almost 2-fold increase in the incidence rate ratio for hepatocellular carcinoma between 1975 to 1978 and 1996 to 1998.
The incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men 45 to 54 years of age. These findings are consistent with a true increase and could be explained by consequences of hepatitis C virus acquired during the 1960s and 1970s.
Background and Aims
It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained ...stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known.
Methods
Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992–1995, 1996–1999, 2000–2003, 2004–2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC.
Results
The AA-IR of ICC was 0.92 in 1992–1995 and 0.93 in 2004–2007, while the AA-IR of ECC increased from 0.70 in 1992–1995 to 0.95 in 2004–2007. There was no significant trend in AA-IR of ICC (
p
= 0.07), while there was a significant increase in ECC across the 4-year time periods (
p
< 0.001). Klatskin tumors comprised 6.7 % of CCs with approximately 90 and 45 % misclassified as ICC during 1992–2000 and 2001–2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors.
Conclusions
The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.
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